Human variability in selected large pedigrees will be studied and analyzed with a view to determining how much of it is due to genetic influences, and where possible the mode of genetic action determined. New statistical techniques will be devised for this purpose, allowing for both qualitative and quantitative multifactorial traits, multiple-generation data. Appropriate computer programs will be written, and applied both to data that have already been collected and to data that will be collected with the special purpose of identifying major genes for such traits. The possible existence of such major genes will be demonstrated by segregation analysis and by searching for linkage relationships between such genes and marker genes in blood. This will lead to a more complete understanding of the determinants involved in such diseases as hyperlipidemia, hypertension and cancer.